Eurartesim® (dihydroartemisinin-piperaquine)

Eurartesim® is a fixed-dose combination of dihydroartemisinin-piperaquine (DHA-PQP), developed by Alfasigma S.p.A. in partnership with MMV, for the treatment of uncomplicated P. falciparum malaria. It is administered once a day over 3 days. Studies have shown that Eurartesim’s long half-life affords patients a useful period of protection from new malaria infections.1,2

In October 2011, the EMA granted marketing authorization for Eurartesim. In October 2015, Eurartesim was prequalified by WHO and, in June 2017, DHA-PQP was added to the World Health Organization’s Model List of Essential Medicines (EML) and Model List of Essential Medicines for Children (EMLc) after a successful application to the EML by Alfasigma.

In 2015, Alfasigma entered into an exclusive licensing agreement with Pierre Fabre to expand its ability to support country registration requirements and national adoption of Eurartesim in 32 African countries. MMV, Alfasigma and Pierre Fabre are working closely with normative bodies, financing entities, and national/international implementing partners to ensure appropriate product introduction and use of Eurartesim in malaria-endemic countries.

Alfasigma will submit a regulatory dossier to the EMA for a new dispersible formulation of Eurartesim designed specifically to address the treatment needs of children.

Access in Action

Cambodia, situated at the epicentre of emerging resistance to many existing antimalarials, was the first malaria-endemic country to place an order for Eurartesim. Cambodia adopted DHA-PQP as first-line treatment for malaria in 2012.

Four African countries (Burkina Faso, Ghana, Mozambique, and Tanzania) hosted the INESS phase IV programme, which evaluates post-launch safety and effectiveness of new ACTs. MMV worked closely with Alfasigma and the INESS Principal Investigators to ensure that Eurartesim was registered and available in the INESS countries, in order to support the INESS focus on evaluating the cardiac safety of Eurartesim. The safety results of the INESS study published in 20153 showed that Eurartesim was generally well-tolerated. No association between QT interval prolongation and clinical signs and symptoms of cardiotoxicity was identified in patients taking Eurartesim.

MMV has worked with Alfasigma to design patient-friendly packaging to facilitate the correct use of Eurartesim and to ensure alignment with distinct packaging requirements customized to special programmatic uses.

There is a growing interest in DHA-PQP as a tool for potential use in mass-drug-administration (MDA) campaigns supporting national elimination efforts. In Zambia, elimination pilot work, supported by the Bill & Melinda Gates Foundation, has been carried out by the Government of Zambia in collaboration with the Malaria Control and Elimination Partnership in Africa (MACEPA). MMV contributed to the development of training materials for the MDA pilot and worked closely with Alfasigma to ensure timely and sufficient availability of Eurartesim to support programme requirements. Similar work has been undertaken in Mozambique through the MALTEM project with potential extension to other districts. These MDA pilots have reinforced the need for enhanced pharmacovigilance during the use of ACTs for mass-drug administration across whole communities.

In parallel, there is growing interest amongst the research community in DHA-PQP as a possible alternative for intermittent preventive treatment in pregnancy (IPTp). MMV, via a collaboration with the London School of Hygiene and Tropical Medicine, is supporting a study to evaluate the cardiac safety of DHA-PQP in pregnant women compared to SP, the current standard of care for IPTp. This study will also assess the pharmacokinetics of DHA-PQP in pregnancy.

MMV is collaborating with the Liverpool School of Tropical Medicine (LSTM) to generate additional safety data for the use of DHA-PQP during the first trimester of pregnancy. This work is a dual-phase observational study in Indonesia carried out by the Timika Research Facility. The study started in October 2017 and will involve retrospective and prospective analysis of DHA-PQP use during the first trimester of pregnancy.

A phase IIIb, open label trial, to generate evidence on the safety and efficacy in paediatric patients in India, and permit its local registration, was launched in December 2015 and recruitment completed in early 2017. Evidence from this study will be critical for informing future policy-making regarding recommended first-line treatments for P. falciparum malaria in India.

DHA-PQP has recently been included as a recommended treatment for uncomplicated malaria treatment in Burkina Faso’s national treatment guidelines. Subsequently, the Ministry of Health has elected to include this medicine alongside artemether-lumefantrine and pyronaridine-artesunate in a pilot assessing the feasibility of implementing multiple first-line therapies (MFTs). The 2-year project was kicked off in late 2017.

The protective potential of DHA-PQP in HIV-infected pregnant women will also be assessed in Mozambique and Gabon with our partners from IS Global in a 2-year study. MMV will be supporting the analysis of the pharmacokinetic data.

Over 4.5 million treatments of Eurartesim have been distributed since approval by the EMA.

Past and current partners:

Alfasigma S.p.A, INDEPTH Effectiveness and Safety Studies (INESS), Malaria Control and Elimination Partnership in Africa (MACEPA), Liverpool School of Tropical Medicine, Ministry of Health Cambodia (National Center for Malaria Control, Parasitology and Entomology – CNM; and the Department of Drugs and Food – DDF), Pierre Fabre, Population Services International (Cambodia and Kenya), The Global Fund to Fight AIDS Tuberculosis and Malaria, World Health Organization (WHO – Geneva and Cambodia).